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A retained intron in the 3′‐ UTR of Calm3 mRNA mediates its Staufen2‐ and activity‐dependent localization to neuronal dendrites
Author(s) -
Sharangdhar Tejaswini,
Sugimoto Yoichiro,
HeraudFarlow Jacqueline,
FernándezMoya Sandra M,
Ehses Janina,
Ruiz de los Mozos Igor,
Ule Jernej,
Kiebler Michael A
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744334
Subject(s) - messenger rna , microbiology and biotechnology , untranslated region , three prime untranslated region , intron , chemistry , biology , gene , biochemistry
Dendritic localization and hence local mRNA translation contributes to synaptic plasticity in neurons. Staufen2 (Stau2) is a well‐known neuronal double‐stranded RNA ‐binding protein (ds RBP ) that has been implicated in dendritic mRNA localization. The specificity of Stau2 binding to its target mRNA s remains elusive. Using individual‐nucleotide resolution CLIP ( iCLIP ), we identified significantly enriched Stau2 binding to the 3′‐ UTR s of 356 transcripts. In 28 (7.9%) of those, binding occurred to a retained intron in their 3′‐ UTR . The strongest bound 3′‐ UTR intron was present in the longest isoform of Calmodulin 3 ( Calm3 L ) mRNA . Calm3 L 3′‐ UTR contains six Stau2 crosslink clusters, four of which are in this retained 3′‐ UTR intron. The Calm3 L mRNA localized to neuronal dendrites, while lack of the 3′‐ UTR intron impaired its dendritic localization. Importantly, Stau2 mediates this dendritic localization via the 3′‐ UTR intron, without affecting its stability. Also, NMDA ‐mediated synaptic activity specifically promoted the dendritic mRNA localization of the Calm3 L isoform, while inhibition of synaptic activity reduced it substantially. Together, our results identify the retained intron as a critical element in recruiting Stau2, which then allows for the localization of Calm3 L mRNA to distal dendrites.